Effects of vonoprazan and proton pump inhibitors on the efficacy of bevacizumab: a multicentre retrospective study

Kenta Yagi, Akinori Maruo, Shunsuke Ishida, Fuka Aizawa, Soichiro Ushio, Satoshi Sakaguchi, Makoto Kajizono, Takahiro Niimura, Mitsuhiro Goda, Hirofumi Hamano, Yuki Izawa-Ishizawa, Yoshito Zamami, Keisuke Ishizawa

Research output: Contribution to journalArticlepeer-review


Gastric acid secretion inhibitors such as proton pump inhibitors (PPIs) and vonoprazan may change the duration of treatment with bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor, for cancer. However, there are no data on this prolongation effect. Here, we aimed to determine whether the use of PPIs or vonoprazan in patients with cancer receiving bevacizumab affected the duration of bevacizumab treatment. This observational study was conducted at two national university hospitals in Japan and involved 222 patients using oral PPIs (N = 190) or vonoprazan (N = 32) at the start of bevacizumab treatment between January 2015 and December 2018. Patients who received only one course of bevacizumab were excluded. The primary endpoint was the duration of bevacizumab treatment. The duration of bevacizumab treatment varied significantly between the PPI and vonoprazan groups. For cancer types other than colorectal cancer (breast, lung, brain, and ovarian cancers), the median duration of treatment was 217 days (p < 0.05) and was longer in the vonoprazan group than in the PPI group. However, for colorectal cancer, the median duration of bevacizumab treatment was 147 days longer in the PPI group than in the vonoprazan group. Selection of appropriate gastric acid secretion inhibitors may improve the therapeutic efficacy of anti-VEGF drugs, including bevacizumab. Oestrogen is a key regulator of this effect and may be responsible for the varying association between PPI or vonoprazan administration and the difference in bevacizumab treatment duration between colon cancer and other cancer types.

Original languageEnglish
JournalClinical and Experimental Medicine
Publication statusAccepted/In press - 2023


  • Bevacizumab
  • Cancer
  • Proton pump inhibitor
  • Vonoprazan

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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